Therapeutic impact of human serum albumin-thioredoxin fusion protein on influenza virus-induced lung injury mice.
Therapeutic impact of human serum albumin-thioredoxin fusion protein on influenza virus-induced lung injury mice.
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DOI：
10.3389/fimmu.2014.00561
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发表时间：
2014
影响因子：
7.3
通讯作者：
Otagiri M
中科院分区：
文献类型：
--
作者：
Tanaka R;Ishima Y;Enoki Y;Kimachi K;Shirai T;Watanabe H;Chuang VT;Maruyama T;Otagiri M
活性氧(ROS)是病毒性肺部感染产生的主要致病分子。我们曾报道使用重组人血清白蛋白(HSA)-硫氧还蛋白1(TRX)融合蛋白(HSA-TRX)来延长TRX的半衰期，TRX是一种具有抗氧化特性的内源性蛋白。因此，有可能克服TRX不良的药代动力学和短暂的药理作用。我们假设HSA-TRX将减弱流感病毒感染期间中性粒细胞增加的ROS产生，如羟基自由基。以8-羟基-2‘-脱氧鸟苷和3-硝基酪氨酸水平作为HSA-Trx抗氧化活性的指标。此外，还检测了HSA-Trx对PR8(H1N1)流感病毒诱导的小鼠肺损伤的细胞保护作用。结果表明，HSA-Trx可降低流感病毒致肺损伤小鼠BALF中的细胞总数、中性粒细胞数和总蛋白。HSA-Trx治疗可显著降低病毒感染小鼠肺组织中8-羟基-2‘-脱氧鸟苷和3-硝基酪氨酸的水平，但不能抑制诱导型一氧化氮合酶的表达。另一方面，达菲®治疗还显著抑制了炎症细胞的产生和中性粒细胞的渗透，以及BALF中的蛋白水平和流感病毒引起的肺组织病理变化。达菲的抑制作用略强于HSA-TRX。有趣的是，达菲显著抑制了病毒的增殖，而HSA-TRX则没有任何作用。这些结果表明，HSA-TRX可能通过抑制炎症细胞反应和抑制肺内NO的过量产生，对流感病毒肺炎等各种急性炎症性疾病具有治疗价值。
Reactive oxygen species (ROS) are the primary pathogenic molecules produced in viral lung infections. We previously reported on the use of a recombinant human serum albumin (HSA)–thioredoxin 1 (Trx) fusion protein (HSA–Trx) for extending the half-life Trx, an endogenous protein with anti-oxidant properties. As a result, it was possible to overcome the unfavorable pharmacokinetic and short pharmacological properties of Trx. We hypothesized that HSA–Trx would attenuate the enhanced ROS production of species such as hydroxyl radicals by neutrophils during an influenza viral infection. The levels of 8-hydroxy-2′-deoxyguanosine and 3-nitrotyrosine were used as indices of the anti-oxidant activity of HSA–Trx. In addition, the cytoprotective effects of HSA–Trx were examined in PR8 (H1N1) influenza virus-induced lung injured mice. The findings show that HSA–Trx reduced the number of total cells, neutrophils, and total protein in BALF of influenza virus-induced lung injured mice. The HSA–Trx treatment significantly decreased the level of 8-hydroxy-2′-deoxyguanosine and 3-nitrotyrosine, but failed to inhibit inducible nitric oxide synthase expression, in the lungs of the virus-infected mice. On the other hand, Tamiflu® treatment also significantly suppressed the production of inflammatory cells and neutrophil infiltration, as well as the protein level in BALF and lung histopathological alterations caused by the influenza virus. The suppressive effect of Tamiflu® was slightly stronger than that of HSA–Trx. Interestingly, Tamiflu® significantly decreased virus proliferation, while HSA–Trx had no effect. These results indicate that HSA–Trx may be of therapeutic value for the treatment of various acute inflammatory disorders such as influenza-virus-induced pneumonia, by inhibiting inflammatory-cell responses and suppressing the overproduction of NO in the lung.
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影响因子：
6.7
作者：
Vlahos R;Stambas J;Bozinovski S;Broughton BR;Drummond GR;Selemidis S
通讯作者：
Selemidis S
影响因子：
5.1
作者：
Hashiba, T;Suzuki, M;Ishigatubo, Y
通讯作者：
Ishigatubo, Y
影响因子：
4.8
作者：
Andersen, Jan Terje;Pehrson, Rikard;Ekblad, Caroline
通讯作者：
Ekblad, Caroline
DOI：
10.1152/ajplung.2001.280.1.l69
发表时间：
2001-01-01
影响因子：
4.9
作者：
Suliman, HB;Ryan, LK;Folz, RJ
通讯作者：
Folz, RJ
影响因子：
6.1
作者：
Ueda, Shugo;Nakamura, Takayuki;Nakamura, Hajime
通讯作者：
Nakamura, Hajime